Inhibition shapes response selectivity in the inferior colliculus by gain modulation

Abstract

Pharmacological block of inhibition is often used to determine if inhibition contributes to spike selectivity, in which a preferred stimulus evokes more spikes than a null stimulus. When inhibitory block reduces spike selectivity, a common interpretation is that differences between the preferred- and null-evoked inhibitions created the selectivity from less-selective excitatory inputs. In models based on empirical properties of cells from the inferior colliculus (IC) of awake bats, we show that inhibitory differences are not required. Instead, inhibition can enhance spike selectivity by changing the gain, the ratio of output spikes to input current. Within the model, we made preferred stimuli that evoked more spikes than null stimuli using five distinct synaptic mechanisms. In two cases, synaptic selectivity (the differences between the preferred and null inputs) was entirely excitatory, and in two it was entirely inhibitory. In each case, blocking inhibition eliminated spike selectivity. Thus, observing spike rates following inhibitory block did not distinguish among the cases where synaptic selectivity was entirely excitatory or inhibitory. We then did the same modeling experiment using empirical synaptic conductances derived from responses to preferred and null sounds. In most cases, inhibition in the model enhanced spike selectivity mainly by gain modulation and firing rate reduction. Sometimes, inhibition reduced the null gain to zero, eliminating null-evoked spikes. In some cases, inhibition increased the preferred gain more than the null gain, enhancing the difference between the preferred- and null-evoked spikes. Finally, inhibition kept firing rates low. When selectivity is quantified by the selectivity index (SI, the ratio of the difference to the sum of the spikes evoked by the preferred and null stimuli), inhibitory block reduced the SI by increasing overall firing rates. These results are consistent with inhibition shaping spike selectivity by gain control.

Keywords: directional selectivity; gain control; inhibition; modeling; response selectivity; spike threshold.

Figure 1

Measured and modeled current-step responses match. (A) in vivo (left) and model cell (right) potentials (top) for a sustained cell stimulated with current steps (bottom). Scale bars and step sizes also apply to (B). (B) Same as (A) for an onset cell. (C) Empirical and model I/O functions for average response of each cell type.

Figure 2

Blocking inhibition can eliminate spike selectivity independent of the underlying mechanism of synaptic selectivity. Spike selectivity is generated by five different mechanisms of synaptic selectivity in a modeled sustained cell (A–E) and onset cell (F–J). Each mechanism had differences in only one synaptic conductance parameter, as shown. In each case, the preferred conductance pair evoked one spike and the null-evoked no spikes (selectivity index SI = 1). Removing inhibition eliminated spike selectivity (SI = 0) in every example.

Figure 3

Inhibition enhances FM selectivity by controlling the gain, example cell. (A) Measured and computed responses to 100, 200, and 300 pA current steps (50 ms shown). Right: measured and computed I/O functions. (B) Measured membrane potentials (top) in response to preferred (downward, single trace) and null (upward, average of 10 traces) FMs and the derived FM-evoked synaptic conductance (bottom). Spike probability and SI as shown. (C–E) Using the model cell from (A) and the control excitations shown in (B), we computed membrane responses using (C) the control inhibitions, (D) the average of the preferred and null inhibitions, and (E) no inhibition. Model firing probabilities and SIs as shown.

Figure 4

Inhibition enhances FM selectivity by controlling gain, summary. (A) Average modeled and measured I/O curves. (B) Measured FM-evoked spike probability plotted against spike probability computed in the models using the derived FM-evoked conductance pairs. (C) Selectivity index (SI) for all eight FM sets, modeled vs. measured. (D) Computed spike probability, with and without inhibition. (E) The change in computed spikes/trial following the elimination of inhibition. The change is equal to the spikes/trial under control conditions with inhibition intact subtracted from the spikes/trial with no inhibition. (F) Selectivity index computed using either the control conductance sets, conductance sets with the average inhibition and the control excitations, or with the control excitations only. Red lines indicate no change in SI using the average inhibition.

Figure 5

Inhibition enhances spike selectivity by modulating gain, schematic. Input/output (I/O) schematics illustrate three scenarios in which inhibition enhances spikes selectivity by reducing spike rates and controlling gain, the ratio of output/input. In each panel, the solid black line represents the I/O curve, the dashed vertical lines represent the input current for the control condition (tall and thick for preferred; short and thin for null), and the red lines represent the input current with no inhibition. Inhibition enhances spike selectivity by: (A) keeping the inputs below saturation; (B) keeping the inputs in the steepest part of the I/O curve; (C) keeping the firing rates low; and (D) keeping the null input below threshold, where the gain is zero. In (C), it is not required for inhibition to change the gain to enhance spike selectivity, although, it does in this example.